Meso-sized capsules useful for the delivery of agricultural chemicals

ABSTRACT

Disclosed herein are mesocapsules that include agriculturally active ingredients. These mesocapsules are comprised of a polyurea shell and include hydrophilic groups on their surfaces and have a volume-average diameter of about 500 nm or less and some of them have a volume-average diameter on the order of about 300 nm or less. These mesocapsules are suited for delivering active ingredients that are not very soluble in water. Methods for making these mesocapsules include interfacial polycondensation reactions carried out in the presence of surfactants and other methods in which all or most of the surfactant is replaced by adding amino acids to the aqueous phase of the interfacial reaction mixture before forming the final emulsion.

CROSS-REFERENCE TO RELATED APPLICATIONS

This Application claims the benefit of U.S. Provisional Application61/232,044 filed on Aug. 7, 2009, which is expressly incorporated byreference herein.

FIELD OF THE INVENTION

Various aspects relate to materials and methods for making meso-sizedcapsules and using them to deliver active ingredients such asfungicides, insecticides, miticides, herbicides, safeners and modifiersof plant physiology or structure to plants.

BACKGROUND

Modern agricultural pesticide active ingredients including fungicides,insecticides miticides, herbicides and safeners as well as modifiers ofplant physiology and structures and nutrients are typically formulatedas liquid or solid formulations. These formulations are designed so thatthey are convenient for the grower or end user to use and so that theinherent biological activity of the active ingredient is properlyexpressed. The purpose of various aspects and embodiments disclosedherein is to further improve the effectiveness and efficiency of thedelivery and biological activity of active ingredients used inagriculture and general pest management.

DEFINITIONS

The term “agricultural active ingredient (AI)” as used herein refers toa chemical used in agriculture, horticulture and pest management forprotection of crops, plants, structures, humans and animals againstunwanted organisms such as fungal and bacterial plant pathogens, weeds,insects, mites, algae, nematodes and the like. Specifically, activeingredients used for these purposes include fungicides, bactericides,herbicides, insecticides, miticides, algaecides, nemtocides andfumigants. The term “agricultural active ingredient” also includesinsect attractants, repellants and pheromones, modifiers of plantphysiology or structure and herbicide safeners.

The term “meso” as used herein describes particles, capsules, ordroplets which have a volume-average diameter of between about 30 nm andabout 500 nm. The term “mesocapsule” as used herein describes capsulesor core-shell particles having a volume-average diameter of betweenabout 30 nm and about 500 nm.

The term “about” means a range of plus to minus 10 percent, e.g. about 1included values from 0.9 to 1.1.

The term “poorly water soluble” as used herein means active ingredientswith solubility in water of less than about 1000 ppm. Preferably, thepoorly water soluble active ingredient has a solubility in water of lessthan 100 ppm, more preferably less than 10 ppm.

The term “water immiscible solvent” as used herein means a solvent ormixture of solvents with a solubility in water of about 10 g/100 ml orless.

The term “essentially no surfactant” as used herein means a surfactantconcentration of less than 1 weight percent with respect to the oilphase and more preferably less than 0.5 weight percent of a surfactantwith respect to the oil phase.

The term “surfactant” as used herein means a substance used to createand/or stabilize an emulsion. Surfactants include nonionic, anionic,cationic, or combinations of nonionic and anionic or nonionic andcationic. Examples of suitable surfactants include alkali metal laurylsulfates such as sodium dodecyl sulfate, alkali metal fatty acids saltssuch as sodium oleate and sodium stearate, alkali metal alkylbenzenesulfonates such as sodium dodecylbenzene sulfonate, polyoxyethylenenonionics, and quaternary ammonium surfactants. Standard referencesources from which one of skill in the art can select suitablesurfactants, without limitation to the above mentioned classes, includeHandbook of Industrial Surfactants, Fourth Edition (2005) published bySynapse Information Resources Inc, and McCutcheon's Emulsifiers andDetergents, North American and International Editions (2008) publishedby MC Publishing Company.

The term “interfacial condensation” as used herein means a reactionbetween two complimentary, organic intermediates that takes place at aninterface between two immiscible liquids in which one immiscible liquidis dispersed in the other immiscible liquid. An example of aninterfacial condensation reaction is given by U.S. Pat. No. 3,577,515which is expressly incorporated by reference herein. A “core-shell”capsule is a capsule created by an interfacial condensation reactionthat takes place between two immiscible phases in which the firstimmiscible phase is a dispersed phase, the second immiscible phase is acontinuous phase; and the dispersed phase or core is encapsulated withina shell formed by the reaction of two complimentary, organicintermediates which form the shell and the core-shell capsule isdispersed within the continuous phase.

The term “crosslinker” as used herein means a substance that initiatesand facilitates reaction of polymer precursors to form a core shellparticle. The crosslinker becomes part of the polymer structurecomprising the core shell particle. Examples of crosslinkers as usedherein include water, water-soluble diamines, water soluble polyamines,water soluble polyamino acids, water soluble diols, water solublepolyols, and mixtures thereof.

SUMMARY

One embodiment of the present disclosure includes a composition for thedelivery of an agricultural active ingredient, comprising a mesocapsule,the mesocapsule having a polymer shell, and a poorly water solubleagricultural active ingredient, wherein the active ingredient is atleast partially included within the polymer shell, the mesocapsuleshaving a volume-average particle diameter between about 30 nm and about500 nm.

Another embodiment of the present disclosure includes a method forsynthesizing a mesocapsule, comprising the steps of providing an oilphase, the oil phase including at least one agricultural activeingredient and one or more polymer precursers capable of reacting toform a shell, supplying an aqueous phase, the aqueous phase includingwater and at least one crosslinker, adding a surfactant to at least oneof the aqueous phase and the oil phase, mixing the oil and the aqueousphases under shear conditions sufficient to form an emulsion havingmeso-sized droplets with a volume-average diameter of about 500 nm orless, and reacting the polymer precurser with the crosslinker to formthe mesocapsule.

Another embodiment of the present disclosure includes a method forsynthesizing a surfactant free mesocapsule, comprising the steps ofproviding an oil phase, the oil phase including at least oneagricultural active ingredient and at least one polyisocyanate,supplying an aqueous phase, wherein the aqueous phase includes at leastone component wherein the component includes at least one functionalmoiety that is either a primary or secondary amine or a primary orsecondary amino group and additionally at least one hydrophilicfunctional group, mixing the oil and the aqueous phases to form anemulsion, and reacting polyisocyanate with a crosslinker to form themesocapsule.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 summarizes the components of stock solutions of glycine andlysine that were prepared and used to synthesize the exemplarymeso-sized capsules disclosed herein.

FIG. 2 summarizes the ingredients that were combined in order tosynthesize the exemplary mesocapsules of fenbuconazole disclosed herein.

FIG. 3 summarizes the ingredients that were combined in order tosynthesize exemplary mesocapsules of herbicides, fungicides andinsecticides disclosed herein.

FIG. 4 includes a list of exemplary formulations tested for theireffectiveness as pesticides; the table lists the formulations andprovides an estimate of the wt. % of agricultural active ingredient (AI)in each formulation.

FIG. 5 summarizes the results of testing various formulations identifiedin FIG. 4 for their ability to cure fungal infections caused by Septoriatritici on plants.

FIG. 6 summarizes the results of testing various formulations identifiedin FIG. 4 for their ability to prevent fungal infections caused bySeptoria tritici in plants.

FIG. 7 summarizes the results of testing various formulations identifiedin FIG. 4 for their ability to prevent fungal infections caused byPuccinia recondita f sp. tritici in plants.

FIG. 8 summarizes the results of testing various atrazine formulationsidentified in FIG. 4 for their ability to control weeds. Data arepercent weed control.

FIG. 9 summarizes the results of testing various fluoroxypyr-meptylformulations identified in FIG. 4 for their ability to control weeds.Data are percent weed control.

FIG. 10 summarizes the results of testing various indoxacarbformulations identified in FIG. 4 for their ability to reduce leaffeeding by Diamondback moth.

FIG. 11 summarizes the results of testing various indoxacarbformulations identified in FIG. 4 for their ability to cause Diamondbackmoth mortality.

FIG. 12 summarizes the results of testing various indoxacarbformulations identified in FIG. 4 for their ability to cause Germancockroach mortality when administered by injection.

FIG. 13 summarizes the results of testing various indoxacarbformulations identified in FIG. 4 for their ability to cause Germancockroach mortality when administered by topical application.

FIG. 14 summarizes the results of testing various indoxacarbformulations identified in FIG. 4 for their ability to cause feedingcessation by German cockroach when administered by bait ingestion.

DESCRIPTION

For the purposes of promoting an understanding of the principles of thenovel technology, reference will now be made to the preferredembodiments thereof, and specific language will be used to describe thesame. It will nevertheless be understood that no limitation of the scopeof the novel technology is thereby intended, such alterations,modifications, and further applications of the principles of the noveltechnology being contemplated as would normally occur to one skilled inthe art to which the novel technology relates.

Discovering, developing and producing effective and economicalagricultural active ingredients (AIs) such as fungicides, insecticides,herbicides, safeners, modifiers of plant physiology or structure, andthe like is only part of the challenge facing the agriculture chemicalindustry. It is also important to develop effective formulations ofthese types of compounds to enable their efficient and economicalapplication. Cost considerations alone dictate an ever-growing need fornew formulations and methods for making and using AIs. This need isespecially acute when the effectiveness of AIs is limited or when theyare difficult to handle and apply effectively as desired due to problemssuch as low solubility in aqueous solutions or poor bioavailability inand on plants and insects.

As used herein, the terms ‘plant’ and ‘agricultural crop’ shall mean anycommercially propagated plant whether produced by conventional plantbreeding, vegetative propagation or by employing techniques of geneticmodification.

One of the most effective ways of improving the efficacy of AIs is toincrease the penetration of the AIs' into the plant either through theroot system or through the stem and leaf surfaces or into an insectthrough the gut or exoskeleton. Often times this involves formulatingthe AIs in a water soluble form. However, many otherwise effective AIsare not very soluble in water. Accordingly, a compound or formulationthat increases the penetration of poorly water soluble AIs into andthrough plants and insects has the potential to improve overalleffectiveness of a wide variety of AIs including, for example, AIs thatare not very soluble in water.

Some aspects and embodiments disclosed herein increase an agriculturalactive ingredient's bioavailability by encapsulating the AI into apolyurea core-shell particle of very small size e.g., a mesocapsulehaving a volume-average particle diameter of about 500 nm or less; insome embodiments the mesocapsules diameter is on the order of 300 nm orless. Some of these mesocapsules include a surface functionalized withbiologically compatible hydrophilic functional groups such as carboxylicacid groups. In many applications AIs at least partially encapsulated inmesocapsules more effectively penetrate plants and insects and are moreefficiently transported within the plant and through the plant than areAI's that are not encapsulated.

In addition to their utility for formulating and delivering pesticidalactive ingredients, many of the mesocapsules and methods for makingmeso-sized encapsulated formulations disclosed herein have utility whenused in combination with other active ingredients such as biocides,inks, sunscreens, flavoring ingredients, perfumes, cosmetics,pharmaceuticals and the like. These mesocapsules and methods of makingthe same disclosed herein may also be useful in the delivery of nucleicacid polymers such as double or single stranded DNA or RNA, and/orprotein molecules. These formulations have a wide range of applicationsincluding genetic engineering, diagnostics and therapeutics, e.g.vaccination, and the like.

Core-shell mesocapsules can be prepared by a number of methods includinginterfacial polymerization at the surface of a droplet or particle. Apreferred encapsulating polymer is polyurea including those formed fromthe reaction of a polyisocyanate with a polyamine, a poly amino acid, orwater. Other preferred encapsulating polymers include those formed frommelamine-formaldehyde or urea-formaldehyde condensates, as well assimilar types of aminoplasts. Capsules having shell walls comprised ofpolyurethane, polyamide, polyolefin, polysaccaharide, protein, silica,lipid, modified cellulose, gums, polyacrylate, polyphosphate,polystyrene, and polyesters or combinations of these materials can alsobe used to form core-shell mesocapsules.

Suitable polymers for use in forming mesocapsules in the presentdisclosure include amino-based prepolymers such as urea-, melamine-,benzoguanamine-, and glycouril-formaldehyde resins anddimethyloldihydroxyethylene urea type prepolymers. These prepolymers canbe used as blends and cross linkers with polyvinyl alcohol, polyvinylamines, acrylates (acid functionality preferred), amines,polysaccharides, polyureas/urethanes, poly amino acids, and proteins.Other suitable polymers include polyesters, including biodegradablepolyesters, polyamides, polyacrylates and polyacrylamides, polyvinylpolymer and copolymers with polyacrylates, polyurethanes, polyethers,polyureas, polycarbonates, naturally occurring polymers such as,polyanhydrides, polyphosphazines, polyoxazolines, and UV-curedpolyolefins.

In one embodiment, a poorly water soluble agricultural active ingredientis encapsulated within a core-shell particle of very small size e.g., ofabout 500 nm or less, more preferably 300 nm or less. AIs encapsulatedin these mesocapsules may exhibit increased penetration into insects andplants, plant tissue, plant cells and even plant pathogens than AIs thatare not associated with mesocapsules.

In one embodiment the mesocapsule includes hydrophilic functional groupsbuilt into the polyurea shell and at least partially exposed on themesocapsule's surface. A partial listing of some of the functionalmaterials that can be used to form these particles can be found in thefollowing publication, WO2001/94001, which is incorporated herein byreference in its entirety. Hydrophilic functional groups includecarboxylate, salts of carboxylate, phosphonate, salts of phosphonate,phosphate, salts of phosphate, sulfonate, salts of sulfonate, quaternaryammonium, betaine, oxyethylene or oxyethylene-containing polymers.Preferably, the hydrophilic group is a carboxylate or the salt of acarboxylate.

In one embodiment, the agricultural active ingredient is at least oneagricultural chemical selected from the group consisting of fungicides,insecticides, miticides, herbicides, safeners and modifiers of plantphysiology or structure.

In one embodiment, the agricultural active ingredient has solubility inwater on the order of about 1,000 parts per million or less, preferably100 parts per million or less, and more preferably 10 parts per millionor less.

In one embodiment, the invention is a method for synthesizing amesocapsule, comprising the steps of providing an oil phase, the oilphase including at least one active ingredient and at least onepolyisocyanate; supplying an aqueous phase, and adding an emulsifier;and mixing the oil and the aqueous phases under shear sufficient to forman emulsion having meso-sized droplets with a volume-average diameter ofabout 500 nm or less but preferably less than 300 nm; and reacting thepolyisocyanate with at least one crosslinker or water to form themesocapsule.

Some AIs are solid at room temperature and must be dissolved in asolvent before they can be encapsulated within a polyurea mesocapsule.In one embodiment a poorly water-soluble AI is dissolved in a solventthat readily dissolves the AI before adding the oil phase. Suitablesolvents may be one or a mixture of organic solvents that have low watersolubility, i.e. about 10 g/100 ml or less, which includes, but are notlimited to, petroleum fractions or hydrocarbons such as mineral oil,aromatic solvents, xylene, toluene, paraffinic oils, and the like;vegetable oils such as soy bean oil, rape seed oil, olive oil, castoroil, sunflower seed oil, coconut oil, corn oil, cotton seed oil, linseedoil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and thelike; esters of the above vegetable oils; esters of monoalcohols ordihydric, trihydric, or other lower polyalcohols (4-6 hydroxycontaining), such as 2-ethyl hexyl stearate, ethylhexyl benzoate,isopropyl benzoate, n-butyl oleate, isopropyl myristate, propyleneglycol dioleate, di-octyl succinate, di-butyl adipate, di-octylphthalate, acetyl tributyl citrate, triethylcitrate, triethyl phosphate,and the like; esters of mono, di and polycarboxylic acids, such asbenzylacetate, ethylacetate, and the like; ketones, such ascyclohexanone, acetophenone, 2-heptanone, gamma-butyrolactone,isophorone, N-ethyl pyrrolidone, N-octyl pyrrolidone, and the like;alkyldimethylamides, such as dimethylamide of C8 and C10,dimethylacetamide, and the like; alcohols of low water solubility (i.e.about 10 g/100 ml or less) such as benzyl alcohol, cresols, terpineols,tetrahydrofurfurylalcohol, 2-isopropylphenol, cyclohexanol, n-hexanol,and the like. In some cases, an ultrahydrophobe is added to the oilphase, ostensibly to preserve the stability of an emulsion that will becreated later in the process when the oil phase is mixed with an aqueousphase. This additive is a highly water-insoluble material that 1) has anegligible diffusion coefficient and negligible solubility in thecontinuous aqueous phase and 2) is compatible with the dispersed phase.Examples of ultrahydrophobes include long chain paraffins such ashexadecane, polymers such as polyisobutene such as, for example,Indopol™ H15 (INESO Oligomers), polystyrene, polymethylmethacrylate,natural oils such as seed oils, and silicones such as silicone oil ordimethicone. Preferably, the additive is used in an amount not greaterthan 10 weight percent based on the weight of the dispersed phase.

In one embodiment, the polymer precursor within the dispersed phase is apolyisocyanate or a mixture of polyisocyanates. The polyisocyanatereacts with a crosslinker or with water to form a polyurea shell.Examples of polyisocyanates include, but are not limited to, toluenediisocyanate (TDI), diisocyanato-diphenylmethane (MDI), derivatives ofMDI such as polymethylene polyphenylisocyanate that contains MDI, anexample of which is PAPI 27™ polymeric MDI (The Dow Chemical Company),isophorone diisocyanate, 1,4-diisocyanatobutane, phenylene diisocyanate,hexamethylene diisocyanate, 1,3-bis(isocyanatomethyl)benzene,1,8-disocyanatooctane, 4,4′-methylenebis(phenyl isocyanate),4,4′-methylenebis(cyclohexyl isocyanate) and mixtures thereof. Inanother embodiment, suitable polymer precursors in the dispersed phasemay also include but are not limited to diacid chlorides, polyacidchlorides, sulfonyl chlorides, chloroformates, and the like, andmixtures thereof.

The oil and water phases are combined in the presence of a surfactantthat aids in the creation and or stabilization of meso-size droplets ofless than 500 nm but preferable less than 300 nm. The surfactant can beadded to either the oil phase or to the water phase or to both the oiland water phases. Surfactants include nonionic, anionic, cationic, orcombinations of nonionic and anionic or nonionic and cationic. Examplesof suitable surfactants include alkali metal lauryl sulfates such assodium dodecyl sulfate, alkyl metal fatty acids salts such as oleatesand stearates, alkali methyl alkylbenzene sulfonates such as sodiumdodecylbenzene sulfonate, polyoxyethylene nonionics, and quaternaryammonium surfactants. Standard reference sources from which one of skillin the art can select suitable surfactants, without limitation to theabove mentioned classes, include Handbook of Industrial Surfactants,Fourth Edition (2005) published by Synapse Information Resources Inc,and McCutcheon's Emulsifiers and Detergents, North American andInternational Editions (2008) published by MC Publishing Company.

The emulsion can be prepared by a variety of methods, including batchand continuous methods well known in the art. In a preferred method, theemulsion is prepared using an ultra-high shear device such as anultrasonicating device or a high-pressure homogenizer to createmeso-size droplets of less than 500 nm, preferably less than 300 nm.Ultrasonicating devices include standard sonicating equipment containinga ultrasonic probe that is inserted into the formulation to create themeso-size droplets, one representative example being the Sonicator 400from Misonix Sonicators. High-pressure homogenizers use very highpressure, 500 to 20,000 psi, to force fluid through a small opening andcreate the meso-size droplets. Examples of such devices include but arenot limited the EmulsiFlex™ (Avestin, Inc.) devices and theMicrofluidizer™ (Microfluidics) devices.

In one embodiment a polyisocyanate or a mixture of polyisocyanatesreacts with hydroxyl-containing or amine-containing molecules in thecontinuous phase (i.e. water), such as water-soluble diamines, watersoluble polyamines, water soluble polyamino acids, water soluble diols,water soluble polyols, and mixtures thereof, via an interfacialpolycondensation to form a polymeric shell. Examples of these chainextenders or cross-linkers in the aqueous continuous phase may include,but are not limited to, at least one of water soluble diamines, such asethylenediamine, and the like; water soluble polyamines, such asdiethylenetriamine, triethylenetetramine, tetraethylenepentamine,pentaethylenehexamine, and the like; water soluble amino acids havingmore than one isocyanate-reactive functional group, such as L-lysine,arginine, histidine, serine, threonine, polymers or oligomers of theseaminoacids, and the like; water soluble diols or water soluble polyols,such as ethylene glycol, propylene glycol, polyethylene oxide diol,resorcinol, water soluble amino alcohols, such as 2-aminoethanol, andthe like, and guanidine, guanidine compounds, polyamidines andderivatives and mixtures thereof. In one embodiment the water solublephase includes a diamine with a carboxylate functionality (such asL-lysine) which reacts to form a polyurea shell that includescarboxylate functional groups at the surface of the mesocapsule. Thiscarboxylate functionality may be unneutralized or it may be partly orfully neutralized to form a carboxylate salt.

In still another embodiment the diamine or polyamines or theirequivalents, included in the aforementioned exemplary aqueous phase, areomitted from the reaction mixture. In this embodiment the polyisocyanatereacts with water to form a polyurea shell.

Various factors can be adjusted to increase or decrease the interfacialcondensation reaction rate. These factors include, for example,temperature, pH, mixing rate, reaction times, osmotic pressure and ofcourse changing the levels and types of emulsifiers, polymer components,solvents, the addition of catalysts and the like. For an additionaldiscussion of the effect on temperature, catalysts, pH and the like onthese types of reactions see for example U.S. Pat. No. 4,285,750, whichis incorporated herein by reference in its entirety. Additionalinformation on the effect of salts and salt levels on these types ofreactions can be found in publication, WO2006/092409, which isincorporated herein by reference in its entirety.

Some embodiments of the present disclosure can be realized by varyingthe levels of some of the reactants in the reaction mixture, thereaction mixture consisting of a dispersed oil phase and a continuousaqueous phase which are used to form mesocapsules that include at leastone AI. In some embodiments these include, given as weight percent (wt.%) of the oil phase of at least one AI in the range of from about 1.0wt. % to about 90 wt. %, more preferably from about 1.0 wt. % to about80 wt. %; optionally, a solvent suitable for dissolving the AI in therange of from about 1 wt. % to about 90 wt. %, more preferably fromabout 20 wt. % to about 80 wt. %; optionally, an ultrahydrophobe presentin the range of from about 0.5 wt. % to about 10 wt. %, more preferablyfrom about 1.0 wt. % to about 5.0 wt. %; at least one polyisocyanatepresent in the range of from about 1 wt. % to about 30 wt. %, morepreferably from about 5 wt. % to about 20 wt. %; optionally, anemulsifier present in the range of from 0.1 wt. % to about 20 wt. %,more preferably from about 1 wt. % to about 10 wt. % of the oil phase,in which the oil phase makes up on the order of from about 1% to about60% of the total amount of the emulsion.

The aqueous phase of the reaction mixture consists of from about 40 wt.% to about 99 wt. % of the total emulsion and contains from about 60 wt.% to about 90 wt. % water, from about 1 wt. % to about 30 wt. % of oneor more cross-linkers and optionally, from about 0.1 wt. % to about 20wt. % of one or more water soluble surfactants.

Similarly, some of the ingredients used in some of the exemplaryformulations are optional. For example, it is possible to synthesizeeffective mesocapsules in some embodiments without adding the solventand/or the ultrahydrophobe. The addition of these types of optionalcomponents to the reaction mixture is especially useful when the AI is asolid.

As described herein, one method used in encapsulating poorlywater-soluble materials is to create a polyurea core-shell by aninterfacial condensation reaction of a polyisocyanate or a mixture ofpolyisocyanates in the dispersed oil phase with at least one of waterand a water-soluble polyamine in the continuous phase. In order tostabilize the microcapsule against agglomeration and to control the sizeof microcapsule before the reaction, it is often desirable to add one ormore surfactants or colloidal stabilizers to the reaction mixture. Asurfactant may be useful if the goal of the reaction is to createmesocapsules smaller than 500 nm. However, the presence of surfactantmay be detrimental in many end use applications. For example, indelivery of agricultural active ingredients into a plant, the surfactantaccompanying the polyurea mesocapsules may be injurious to the plant. Inother applications, the surfactant may also cause unwanted foaming inthe final product. Accordingly, it may be beneficial to develop a methodfor efficiently synthesizing micro- and mesocapsules that required lessor no surfactant than the methods previously discussed.

One aspect of the present disclosure is a method for producingmicrocapsules or mesocapsules in which a compound is added that includesat least one functional moiety that is either a primary or secondaryamine or a primary or secondary amino group and additionally at leastone hydrophilic functional group, and wherein the addition of thiscomponent allows for an emulsion to be made with essentially nosurfactant. In one embodiment of the invention, the component isglycine, a salt of glycine, or a mixture of glycine and a salt ofglycine. These methods for producing micro- or mesocapsules includeadding glycine, a salt of glycine, or a mixture of glycine and a salt ofglycine to the aqueous phase of the reaction mixture before creating thefinal emulsion, and, if desired, before initiating the cross linkingreaction between components such as polyisocyanate to create thepolyurea mesocapsules shell. Additional molecules that can be used inaddition to or in place of glycine include other molecules that haveeither a primary or secondary amine group on one end and of the moleculeand a hydrophilic group such as a carboxylate or a trimethylamine on theother end of the molecule. It may not be necessary to neutralize all ofthe charged moieties in order to obtain the product formed by theprocesses disclosed herein. A partial list of some of these types ofmolecules can be found in U.S. Pat. No. 4,757,105 which is incorporatedherein by reference in its entirety.

Without wishing to be bound by any single theory or explanation it maybe that adding either the glycine, a glycine salt, or glycine-likematerial before forming the final emulsion allows the glycine to reactwith a small part of the di- or polyisocyanate to create asurfactant-like molecule which aids in the creation and/or thestabilization of the emulsion and helps control the droplet size in thefinal emulsion. Next, after creation of the final emulsion, during theinterfacial condensation reaction, the surfactant-like molecule formedby the reaction of glycine reacts to become incorporated into thepolyurea shell and no longer acts as a free surfactant. The hydrophilicfunctional group of the glycine or glycine like molecule exists at thesurface of the shell to help stabilize the shell.

The present disclosure includes a method for encapsulating poorlywater-soluble AIs within a polyurea core-shell particle using reducedlevels of surfactant or colloidal stabilizer or by using no surfactantor colloidal stabilizer and still maintaining dispersion stability andparticle size control. This present disclosure has applications indelivering agricultural active ingredients where excess surfactant couldhave phytotoxic effects on plants and for other delivery or controlledrelease applications where the presence of a surfactant would bedetrimental in the final application.

Polyurea meso-capsules can be made without surfactant using colloidalstabilizers such as polyvinyl alcohol but it is difficult to controlparticle size. Some formulations of AIs are made using surfactants thatdo not exhibit some of the properties that need to be avoided, such asusing less phytotoxic surfactants or surfactants that exhibit lessfoaming.

Adding a glycine salt or a similar molecule that includes either primaryor secondary amine groups and either a carboxylate group or atrimethylamine to the aqueous phase before creating the final emulsionlowers or eliminates altogether the need to add a surfactant to thereaction mixture. Adding a material that is not a surfactant such asglycine and that reacts with the di- or polyisocyanate to create amolecule that helps to emulsify and stabilize the organic phase and thatfurther reacts into polyurea shell once the di or polyisocyanate,enables the production of mesocapsules that are free or essentially freeof surfactants. In some embodiments essentially free implies that theoil phase includes less than about 1.0 weight percent and morepreferably less than 0.5 weight percent of a surfactant.

Being able to formulate mesocapsules that include no or very littleresidual surfactant has advantages in many applications where thepresence of free surfactant in the formulation has a detrimental orunwanted effect. There may also be a potential cost advantage in casethe amount of expensive surfactant can be reduced.

One embodiment of the invention is a mesocapsule that includes at leastone AI such as, for example, the fungicide fenbuconazole. An exemplarymethod of forming these mesocapsules includes an interfacialpolycondensation reaction between the compound in the oil phase andeither water or water and a water soluble cross linker in the aqueousphase. In order to produce mesocapsules, especially mesocapsules with anaverage diameter of about 500 nm or less or mesocapsules with an averagediameter of about 300 nm or less, either a surfactant such as sodiumdodecyl sulfate can be added to the reaction mixture or a molecule suchas glycine can be added to the aqueous phase before creating the finalemulsion and/or initiating the cross linking reaction. In one embodimentthe oil and aqueous phases are mixed under high-shear to form anemulsion that includes meso-sized droplets which are converted intopolyurea mesocapsules as described herein. Devices for processing theemulsion to help form mesocapsules include ultrasonicating devicesand/or high-pressure homogenizers. Ultrasonicating devices includestandard sonicating equipment containing an ultrasonic probe that isinserted into the system to create the meso-size droplets, onerepresentative example being the Sonicator 400 from Misonix Sonicators.High-pressure homogenizers use very high pressure, 500 to 20,000 psi, toforce fluid through a small opening and create the meso-size droplets.Examples of such devices include the EmulsiFlex™ (Avestin, Inc.) devicesand the Microfluidizer™ (Microfluidics) devices.

In one embodiment a poorly water soluble AI is optionally dissolved in asolvent such as benzyl acetate. Optionally, an ultrahydrophobe such ashexadecane can be added to help preserve the stability of an emulsionthat will form once the oil and water phases are combined. Apolyisocyanate, for example PAPI™ 27 polymeric MDI (The Dow ChemicalCompany) is added to the oil phase. In order to aid in the formation ofmeso-sized droplets which are a precursor to forming mesocapsules asurfactant such as the sodium salt of dodecyl sulphate (SDS) may beadded to either or both the oil or water phases. Alternatively, glycineor any other molecule with either an amine or amino moiety on one end ofthe molecule and a hydrophilic group on the other end of the molecule isadded to the aqueous phase before forming the final emulsion orinitiating the cross-linking reaction. The amount of glycine or similarmolecule can be increased as necessary to replace all or at least someof the surfactant. Next, the oil and water phases are mixed andoptionally processed with an ultra-high shear device such as aMicrofluidizer™ (Microfluidics) device to create the desired smalldroplets, which are converted to mesosized polyurea capsules asdescribed herein.

Many classes and types of insecticides are useful in agriculture andpest management. Examples include insecticides such as antibioticinsecticides such as allosamidin and thuringensin, macrocyclic lactoneinsecticides such as spinosad, spinetoram and 21-butenyl spinosyns;avermectin insecticides such as abamectin, doramectin, emamectin,eprinomectin, ivermectin and selamectin; milbemycin insecticides such aslepimectin, milbemectin, milbemycin oxime and moxidectin; botanicalinsecticides such as anabasine, azadirachtin, d-limonene, nicotine,pyrethrins, cinerins, cinerin I, cinerin II, jasmolin I, jasmolin II,pyrethrin I, pyrethrin II, quassia, rotenone, ryania and sabadilla;carbamate insecticides such as bendiocarb and carbaryl; benzofuranylmethylcarbamate insecticides such as benfuracarb, carbofuran,carbosulfan, decarbofuran and furathiocarb; dimethylcarbamateinsecticides dimitan, dimetilan, hyquincarb and pirimicarb; oximecarbamate insecticides such as alanycarb, aldicarb, aldoxycarb,butocarboxim, butoxycarboxim, methomyl, nitrilacarb, oxamyl, tazimcarb,thiocarboxime, thiodicarb and thiofanox; phenyl methylcarbamateinsecticides such as allyxycarb, aminocarb, bufencarb, butacarb,carbanolate, cloethocarb, dicresyl, dioxacarb, EMPC, ethiofencarb,fenethacarb, fenobucarb, isoprocarb, methiocarb, metolcarb, mexacarbate,promacyl, promecarb, propoxur, trimethacarb, XMC and xylylcarb;dinitrophenol insecticides such as dinex, dinoprop, dinosam and DNOC;fluorine insecticides such as barium hexafluorosilicate, cryolite,sodium fluoride, sodium hexafluorosilicate and sulfluramid; formamidineinsecticides such as amitraz, chlordimeform, formetanate andformparanate; fumigant insecticides such as acrylonitrile, carbondisulfide, carbon tetrachloride, chloroform, chloropicrin,para-dichlorobenzene, 1,2-dichloropropane, ethyl formate, ethylenedibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide,iodomethane, methyl bromide, methylchloroform, methylene chloride,naphthalene, phosphine, sulfuryl fluoride and tetrachloroethane;inorganic insecticides such as borax, calcium polysulfide, copperoleate, mercurous chloride, potassium thiocyanate and sodiumthiocyanate; chitin synthesis inhibitors such as bistrifluoron,buprofezin, chlorfluazuron, cyromazine, diflubenzuron, flucycloxuron,flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron,penfluoron, teflubenzuron and triflumuron; juvenile hormone mimics suchas epofenonane, fenoxycarb, hydroprene, kinoprene, methoprene,pyriproxyfen and triprene; juvenile hormones such as juvenile hormone I,juvenile hormone II and juvenile hormone III; moulting hormone agonistssuch as chromafenozide, halofenozide, methoxyfenozide and tebufenozide;moulting hormones such as α-ecdysone and ecdysterone; moultinginhibitors such as diofenolan; precocenes such as precocene I, precoceneII and precocene III; unclassified insect growth regulators such asdicyclanil; nereistoxin analogue insecticides such as bensultap, cartap,thiocyclam and thiosultap; nicotinoid insecticides such as flonicamid;nitroguanidine insecticides such as clothianidin, dinotefuran,imidacloprid and thiamethoxam; nitromethylene insecticides such asnitenpyram and nithiazine; pyridylmethylamine insecticides such asacetamiprid, imidacloprid, nitenpyram and thiacloprid; organochlorineinsecticides such as bromo-DDT, camphechlor, DDT, pp′-DDT, ethyl-DDD,HCH, gamma-HCH, lindane, methoxychlor, pentachlorophenol and TDE;cyclodiene insecticides such as aldrin, bromocyclen, chlorbicyclen,chlordane, chlordecone, dieldrin, dilor, endosulfan, endrin, HEOD,heptachlor, HHDN, isobenzan, isodrin, kelevan and mirex; organophosphateinsecticides such as bromfenvinfos, chlorfenvinphos, crotoxyphos,dichlorvos, dicrotophos, dimethylvinphos, fospirate, heptenophos,methocrotophos, mevinphos, monocrotophos, naled, naftalofos,phosphamidon, propaphos, TEPP and tetrachlorvinphos; organothiophosphateinsecticides such as dioxabenzofos, fosmethilan and phenthoate;aliphatic organothiophosphate insecticides such as acethion, amiton,cadusafos, chlorethoxyfos, chlormephos, demephion, demephion-O,demephion-S, demeton, demeton-O, demeton-S, demeton-methyl,demeton-O-methyl, demeton-S-methyl, demeton-S-methylsulphon, disulfoton,ethion, ethoprophos, IPSP, isothioate, malathion, methacrifos,oxydemeton-methyl, oxydeprofos, oxydisulfoton, phorate, sulfotep,terbufos and thiometon; aliphatic amide organothiophosphate insecticidessuch as amidithion, cyanthoate, dimethoate, ethoate-methyl, formothion,mecarbam, omethoate, prothoate, sophamide and vamidothion; oximeorganothiophosphate insecticides such as chlorphoxim, phoxim andphoxim-methyl; heterocyclic organothiophosphate insecticides such asazamethiphos, coumaphos, coumithoate, dioxathion, endothion, menazon,morphothion, phosalone, pyraclofos, pyridaphenthion and quinothion;benzothiopyran organothiophosphate insecticides such as dithicrofos andthicrofos; benzotriazine organothiophosphate insecticides such asazinphos-ethyl and azinphos-methyl; isoindole organothiophosphateinsecticides such as dialifos and phosmet; isoxazole organothiophosphateinsecticides such as isoxathion and zolaprofos; pyrazolopyrimidineorganothiophosphate insecticides such as chlorprazophos and pyrazophos;pyridine organothiophosphate insecticides such as chlorpyrifos andchlorpyrifos-methyl; pyrimidine organothiophosphate insecticides such asbutathiofos, diazinon, etrimfos, lirimfos, pirimiphos-ethyl,pirimiphos-methyl, primidophos, pyrimitate and tebupirimfos; quinoxalineorganothiophosphate insecticides such as quinalphos andquinalphos-methyl; thiadiazole organothiophosphate insecticides such asathidathion, lythidathion, methidathion and prothidathion; triazoleorganothiophosphate insecticides such as isazofos and triazophos; phenylorganothiophosphate insecticides such as azothoate, bromophos,bromophos-ethyl, carbophenothion, chlorthiophos, cyanophos, cythioate,dicapthon, dichlofenthion, etaphos, famphur, fenchlorphos, fenitrothion,fensulfothion, fenthion, fenthion-ethyl, heterophos, jodfenphos,mesulfenfos, parathion, parathion-methyl, phenkapton, phosnichlor,profenofos, prothiofos, sulprofos, temephos, trichlormetaphos-3 andtrifenofos; phosphonate insecticides such as butonate and trichlorfon;phosphonothioate insecticides such as imicyafos and mecarphon; phenylethylphosphonothioate insecticides such as fonofos and trichloronat;phenyl phenylphosphonothioate insecticides such as cyanofenphos, EPN andleptophos; phosphoramidate insecticides such as crufomate, fenamiphos,fosthietan, mephosfolan, phosfolan and pirimetaphos;phosphoramidothioate insecticides such as acephate, isocarbophos,isofenphos, methamidophos and propetamphos; phosphorodiamideinsecticides such as dimefox, mazidox, mipafox and schradan; oxadiazineinsecticides such as indoxacarb; phthalimide insecticides such asdialifos, phosmet and tetramethrin; pyrazole insecticides such asacetoprole, ethiprole, fipronil, pyrafluprole, pyriprole, tebufenpyrad,tolfenpyrad and vaniliprole; pyrethroid ester insecticides such asacrinathrin, allethrin, bioallethrin, barthrin, bifenthrin,bioethanomethrin, cyclethrin, cycloprothrin, cyfluthrin,beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin,cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin,zeta-cypermethrin, cyphenothrin, deltamethrin, dimefluthrin, dimethrin,empenthrin, fenfluthrin, fenpirithrin, fenpropathrin, fenvalerate,esfenvalerate, flucythrinate, fluvalinate, tau-fluvalinate, furethrin,imiprothrin, metofluthrin, permethrin, biopermethrin, transpermethrin,phenothrin, prallethrin, profluthrin, pyresmethrin, resmethrin,bioresmethrin, cismethrin, tefluthrin, terallethrin, tetramethrin,tralomethrin and transfluthrin; pyrethroid ether insecticides such asetofenprox, flufenprox, halfenprox, protrifenbute and silafluofen;pyrimidinamine insecticides such as flufenerim and pyrimidifen; pyrroleinsecticides such as chlorfenapyr; ryanodine receptor insecticides suchas flubendiamide, chlorantraniliprole (rynaxypyr) and cyantranilipole;tetronic acid insecticides such as spirodiclofen, spiromesifen andspirotetramat; thiourea insecticides such as diafenthiuron; ureainsecticides such as flucofuron and sulcofuron; sulfoximine insecticidessuch as sulfoxaflor and unclassified insecticides such as closantel,crotamiton, EXD, fenazaflor, fenazaquin, fenoxacrim, fenpyroximate,flubendiamide, hydramethylnon, isoprothiolane, malonoben, metaflumizone,metoxadiazone, nifluridide, pyridaben, pyridalyl, pyrifluquinazon,rafoxanide, triarathene and triazamate. The present inventioncontemplates selecting insecticides from this list with watersolubilities of about 1000 ppm or less and formulating them ascore-shell polyurea meso-capsules. Preferable insecticides are thosewith water solubilities of about 100 ppm or less. More preferableinsecticides are those with water solubilities of 10 ppm or less.Insecticides can be chosen based on water solubilities published incompendia such as The Pesticide Manual Fourteenth Edition, (ISBN1-901396-14-2), which is incorporated herein by reference in itsentirety. Future editions of The Pesticide Manual will also be usefulfor selecting insecticides for incorporation into core-shell polyureameso-capsules.

Many classes and types of fungicides are useful in agriculture. Examplesinclude, ametoctradin, amisulbrom2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol,8-hydroxyquinoline sulfate, antimycin, azaconazole, azoxystrobin,benalaxyl, benomyl, benthiavalicarb-isopropyl,benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl,bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeauxmixture, boscalid, bromuconazole, bupirimate, BYF 1047, calciumpolysulfide, captafol, captan, carbendazim, carboxin, carpropamid,carvone, chloroneb, chlorothalonil, chlozolinate, copper hydroxide,copper octanoate, copper oxychloride, copper sulfate, copper sulfate(tribasic), cuprous oxide, cyazofamid, cyflufenamid, cymoxanil,cyproconazole, cyprodinil, coumarin, dazomet, debacarb, diammoniumethylenebis-(dithiocarbamate), dichlofluanid, dichlorophen, diclocymet,diclomezine, dichloran, diethofencarb, difenoconazole, difenzoquat ion,diflumetorim, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M,dinobuton, dinocap, meptyl dinocap, diphenylamine, dithianon, dodemorph,dodemorph acetate, dodine, dodine free base, edifenphos, enestrobin,epoxiconazole, ethaboxam, ethoxyquin, etridiazole, famoxadone,fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil,fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin, fentinacetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil,flumorph, fluopicolide, fluopyram, fluoroimide, fluoxastrobin,fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol,fluxapyrad, folpet, formaldehyde, fosetyl, fosetyl-aluminium,fuberidazole, furalaxyl, furametpyr, guazatine, guazatine acetates,GY-81, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalilsulfate, imibenconazole, iminoctadine, iminoctadine triacetate,iminoctadine tris(albesilate), ipconazole, iprobenfos, iprodione,iprovalicarb, isoprothiolane, isopyrazam, isotianil, kasugamycin,kasugamycin hydrochloride hydrate, kresoxim-methyl, mancopper, mancozeb,mandipropamid, maneb, mepanipyrim, mepronil, meptyldinocap, mercuricchloride, mercuric oxide, mercurous chloride, metalaxyl, mefenoxam,metalaxyl-M, metam, metam-ammonium, metam-potassium, metam-sodium,metconazole, methasulfocarb, methyl iodide, methyl isothiocyanate,metiram, metominostrobin, metrafenone, mildiomycin, myclobutanil, nabam,nitrothal-isopropyl, nuarimol, octhilinone, ofurace, oleic acid (fattyacids), orysastrobin, oxadixyl, oxine-copper, oxpoconazole fumarate,oxycarboxin, penflufen, pefurazoate, penconazole, pencycuron,pentachlorophenol, pentachlorophenyl laurate, penthiopyrad,phenylmercury acetate, phosphonic acid, phthalide, picoxystrobin,polyoxin B, polyoxins, polyoxorim, potassium bicarbonate, potassiumhydroxyquinoline sulfate, probenazole, prochloraz, procymidone,propamocarb, propamocarb hydrochloride, propiconazole, propineb,proquinazid, prothioconazole, pyraclostrobin, pyraxostrobin, pyrazophos,pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone,pyrometostrobin, pyroquilon, quinoclamine, quinoxyfen, quintozene,Reynoutria sachalinensis extract, sedaxane, silthiofam, simeconazole,sodium 2-phenylphenoxide, sodium bicarbonate, sodiumpentachlorophenoxide, spiroxamine, sulfur, SYP-Z071, SYP-048, SYP-Z048,tar oils, tebuconazole, tebufloquin, tecnazene, tetraconazole,thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil,tolclofos-methyl, tolylfluanid, triadimefon, triadimenol,triazolopyrimidine, triazoxide, tricyclazole, tridemorph,trifloxystrobin, triflumizole, triforine, triticonazole, validamycin,valiphenal, valifenate, vinclozolin, zineb, ziram, zoxamide,(RS)—N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide,1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoro acetone hydrate,1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane,2-(2-heptadecyl-2-imidazolin-1-yl)ethanol,2,3-dihydro-5-phenyl-1,4-dithi-ine 1,1,4,4-tetraoxide,2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride,2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine,4-(2-nitroprop-1-enyl)phenyl thiocyanateme: ampropylfos, anilazine,azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox,bentaluron, benzamacril; benzamacril-isobutyl, benzamorf, binapacryl,buthiobate, cadmium calcium copper zinc chromate sulfate, carbamorph,CECA, chlobenthiazone, chloraniformethan, chlorfenazole, chlorquinox,climbazole, copper bis(3-phenylsalicylate), copper zinc chromate,cufraneb, cupric hydrazinium sulfate, cuprobam, cyclafuramid,cypendazole, cyprofuram, decafentin, dichlone, dichlozoline,diclobutrazol, dimethirimol, dinocton, dinosulfon, dinoterbon,dipyrithione, ditalimfos, dodicin, drazoxolon, EBP, ESBP, etaconazole,etem, ethirim, fenaminosulf, fenapanil, fenitropan, fluotrimazole,furcarbanil, furconazole, furconazole-cis, furmecyclox, furophanate,glyodine, griseofulvin, halacrinate, Hercules 3944, hexylthiofos,ICIA0858, isopamphos, isovaledione, mebenil, mecarbinzid, metazoxolon,methfuroxam, methylmercury dicyandiamide, metsulfovax, milneb,mucochloric anhydride, myclozolin, N-3,5-dichlorophenyl-succinimide,N-3-nitrophenylitaconimide, natamycin,N-ethylmercurio-4-toluenesulfonanilide, nickelbis(dimethyldithiocarbamate), OCH, phenylmercurydimethyldithiocarbamate, phosdiphen, prothiocarb; prothiocarbhydrochloride, pyracarbolid, pyridinitril, pyroxychlor, pyroxyfur,quinacetol; quinacetol sulfate, quinazamid, quinconazole, rabenzazole,salicylanilide, SSF-109, sultropen, tecoram, thiadifluor, thicyofen,thiochlorfenphim, thiophanate, thioquinox, tioxymid, triamiphos,triarimol, triazbutil, trichlamide, UK-2A, derivatives of UK-2A such as,for example,(3S,6S,7R,8R)-8-benzyl-3-(3-(isobutyryloxymethoxy)-4-methoxypicolinamido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-ylisobutyrate which has a CAS Registry Number of 328255-92-1 and will bereferred to herein as 328255-92-1, urbacid, XRD-563, and zarilamid,IK-1140, and propargyl amides. The present invention contemplatesselecting fungicides from this list with water solubilities of about1000 ppm or less and formulating them as core-shell polyureameso-capsules. Preferable fungicides are those with water solubilitiesof about 100 ppm or less. More preferable fungicides are those withwater solubilities of 10 ppm or less. Fungicides can be chosen based onwater solubilities published in compendia such as The Pesticide ManualFourteenth Edition, ISBN 1-901396-14-2, which is incorporated herein byreference in its entirety. Future editions of The Pesticide Manual willalso be useful for selecting fungicides for incorporation intocore-shell polyurea meso-capsules.

Many classes and types of herbicides are useful in agriculture. Examplesinclude amide herbicides such as allidochlor, beflubutamid, benzadox,benzipram, bromobutide, cafenstrole, CDEA, chlorthiamid, cyprazole,dimethenamid, dimethenamid-P, diphenamid, epronaz, etnipromid,fentrazamide, flupoxam, fomesafen, halosafen, isocarbamid, isoxaben,napropamide, naptalam, pethoxamid, propyzamide, quinonamid and tebutam;anilide herbicides such as chloranocryl, cisanilide, clomeprop,cypromid, diflufenican, etobenzanid, fenasulam, flufenacet, flufenican,mefenacet, mefluidide, metamifop, monalide, naproanilide, pentanochlor,picolinafen and propanil; arylalanine herbicides such as benzoylprop,flampropand flamprop-M; chloroacetanilide herbicides such as acetochlor,alachlor, butachlor, butenachlor, delachlor, diethatyl, dimethachlor,metazachlor, metolachlor, S-metolachlor, pretilachlor, propachlor,propisochlor, prynachlor, terbuchlor, thenylchlor and xylachlor;sulfonanilide herbicides such as benzofluor, perfluidone, pyrimisulfanand profluazol; sulfonamide herbicides such as asulam, carbasulam,fenasulam and oryzalin; antibiotic herbicides such as bilanafos; benzoicacid herbicides such as chloramben, dicamba, 2,3,6-TBA and tricamba;pyrimidinyloxybenzoic acid herbicides such as bispyribac andpyriminobac; pyrimidinylthiobenzoic acid herbicides such as pyrithiobac;phthalic acid herbicides such as chlorthal; picolinic acid herbicidessuch as aminopyralid, clopyralid and picloram; quinolinecarboxylic acidherbicides such as quinclorac and quinmerac; arsenical herbicides suchas cacodylic acid, CMA, DSMA, hexaflurate, MAA, MAMA, MSMA, potassiumarsenite and sodium arsenite; benzoylcyclohexanedione herbicides such asmesotrione, sulcotrione, tefuryltrione and tembotrione; benzofuranylalkylsulfonate herbicides such as benfuresate and ethofumesate;carbamate herbicides such as asulam, carboxazole chlorprocarb,dichlormate, fenasulam, karbutilate and terbucarb; carbanilateherbicides such as barban, BCPC, carbasulam, carbetamide, CEPC,chlorbufam, chlorpropham, CPPC, desmedipham, phenisopham, phenmedipham,phenmedipham-ethyl, propham and swep; cyclohexene oxime herbicides suchas alloxydim, butroxydim, clethodim, cloproxydim, cycloxydim,profoxydim, sethoxydim, tepraloxydim and tralkoxydim;cyclopropylisoxazole herbicides such as isoxachlortole and isoxaflutole;dicarboximide herbicides such as benzfendizone, cinidon-ethyl, flumezin,flumiclorac, flumioxazin and flumipropyn; dinitroaniline herbicides suchas benfluralin, butralin, dinitramine, ethalfluralin, fluchloralin,isopropalin, methalpropalin, nitralin, oryzalin, pendimethalin,prodiamine, profluralin and trifluralin; dinitrophenol herbicides suchas dinofenate, dinoprop, dinosam, dinoseb, dinoterb, DNOC, etinofen andmedinoterb; diphenyl ether herbicides such as ethoxyfen; nitrophenylether herbicides such as acifluorfen, aclonifen, bifenox,chlomethoxyfen, chlornitrofen, etnipromid, fluorodifen, fluoroglycofen,fluoronitrofen, fomesafen, furyloxyfen, halosafen, lactofen, nitrofen,nitrofluorfen and oxyfluorfen; dithiocarbamate herbicides such asdazomet and metam; halogenated aliphatic herbicides such as alorac,chloropon, dalapon, flupropanate, hexachloroacetone, iodomethane, methylbromide, monochloroacetic acid, SMA and TCA; imidazolinone herbicidessuch as imazamethabenz, imazamox, imazapic, imazapyr, imazaquin andimazethapyr; inorganic herbicides such as ammonium sulfamate, borax,calcium chlorate, copper sulfate, ferrous sulfate, potassium azide,potassium cyanate, sodium azide, sodium chlorate and sulfuric acid;nitrile herbicides such as bromobonil, bromoxynil, chloroxynil,dichlobenil, iodobonil, ioxynil and pyraclonil; organophosphorusherbicides such as amiprofos-methyl, anilofos, bensulide, bilanafos,butamifos, 2,4-DEP, DMPA, EBEP, fosamine, glufosinate, glyphosate andpiperophos; phenoxy herbicides such as bromofenoxim, clomeprop, 2,4-DEB,2,4-DEP, difenopenten, disul, erbon, etnipromid, fenteracol andtrifopsime; phenoxyacetic herbicides such as 4-CPA, 2,4-D, 3,4-DA, MCPA,MCPA-thioethyl and 2,4,5-T; phenoxybutyric herbicides such as 4-CPB,2,4-DB, 3,4-DB, MCPB and 2,4,5-TB; phenoxypropionic herbicides such ascloprop, 4-CPP, dichlorprop, dichlorprop-P, 3,4-DP, fenoprop, mecopropand mecoprop-P; aryloxyphenoxypropionic herbicides such as chlorazifop,clodinafop, clofop, cyhalofop, diclofop, fenoxaprop, fenoxaprop-P,fenthiaprop, fluazifop, fluazifop-P, haloxyfop, haloxyfop-P,isoxapyrifop, metamifop, propaquizafop, quizalofop, quizalofop-P andtrifop; phenylenediamine herbicides such as dinitramine and prodiamine;pyrazolyl herbicides such as benzofenap, pyrazolynate, pyrasulfotole,pyrazoxyfen, pyroxasulfone and topramezone; pyrazolylphenyl herbicidessuch as fluazolate and pyraflufen; pyridazine herbicides such ascredazine, pyridafol and pyridate; pyridazinone herbicides such asbrompyrazon, chloridazon, dimidazon, flufenpyr, metflurazon,norflurazon, oxapyrazon and pydanon; pyridine herbicides such asaminopyralid, cliodinate, clopyralid, dithiopyr, fluoroxypyr,fluoroxypyr-meptyl, haloxydine, picloram, picolinafen, pyriclor,thiazopyr and triclopyr; pyrimidinediamine herbicides such as iprymidamand tioclorim; quaternary ammonium herbicides such as cyperquat,diethamquat, difenzoquat, diquat, morfamquat and paraquat; thiocarbamateherbicides such as butylate, cycloate, di-allate, EPTC, esprocarb,ethiolate, isopolinate, methiobencarb, molinate, orbencarb, pebulate,prosulfocarb, pyributicarb, sulfallate, thiobencarb, tiocarbazil,tri-allate and vernolate; thiocarbonate herbicides such as dimexano, EXDand proxan; thiourea herbicides such as methiuron; triazine herbicidessuch as dipropetryn, triaziflam and trihydroxytriazine; chlorotriazineherbicides such as atrazine, chlorazine, cyanazine, cyprazine,eglinazine, ipazine, mesoprazine, procyazine, proglinazine, propazine,sebuthylazine, simazine, terbuthylazine and trietazine; methoxytriazineherbicides such as atraton, methometon, prometon, secbumeton, simetonand terbumeton; methylthiotriazine herbicides such as ametryn,aziprotryne, cyanatryn, desmetryn, dimethametryn, methoprotryne,prometryn, simetryn and terbutryn; triazinone herbicides such asametridione, amibuzin, hexazinone, isomethiozin, metamitron andmetribuzin; triazole herbicides such as amitrole, cafenstrole, epronazand flupoxam; triazolone herbicides such as amicarbazone, bencarbazone,carfentrazone, flucarbazone, propoxycarbazone, sulfentrazone andthiencarbazone-methyl; triazolopyrimidine herbicides such ascloransulam, diclosulam, florasulam, flumetsulam, metosulam, penoxsulamand pyroxsulam; uracil herbicides such as butafenacil, bromacil,flupropacil, isocil, lenacil and terbacil; 3-phenyluracils; ureaherbicides such as benzthiazuron, cumyluron, cycluron, dichloralurea,diflufenzopyr, isonoruron, isouron, methabenzthiazuron, monisouron andnoruron; phenylurea herbicides such as anisuron, buturon, chlorbromuron,chloreturon, chlorotoluron, chloroxuron, daimuron, difenoxuron,dimefuron, diuron, fenuron, fluometuron, fluothiuron, isoproturon,linuron, methiuron, methyldymron, metobenzuron, metobromuron, metoxuron,monolinuron, monuron, neburon, parafluoron, phenobenzuron, siduron,tetrafluoron and thidiazuron; pyrimidinylsulfonylurea herbicides such asamidosulfuron, azimsulfuron, bensulfuron, chlorimuron, cyclosulfamuron,ethoxysulfuron, flazasulfuron, flucetosulfuron, flupyrsulfuron,foramsulfuron, halosulfuron, imazosulfuron, mesosulfuron, nicosulfuron,orthosulfamuron, oxasulfuron, primisulfuron, pyrazosulfuron,rimsulfuron, sulfometuron, sulfosulfuron and trifloxysulfuron;triazinylsulfonylurea herbicides such as chlorsulfuron, cinosulfuron,ethametsulfuron, iodosulfuron, metsulfuron, prosulfuron, thifensulfuron,triasulfuron, tribenuron, triflusulfuron and tritosulfuron;thiadiazolylurea herbicides such as buthiuron, ethidimuron, tebuthiuron,thiazafluoron and thidiazuron; and unclassified herbicides such asacrolein, allyl alcohol, azafenidin, benazolin, bentazone,benzobicyclon, buthidazole, calcium cyanamide, cambendichlor,chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, cinmethylin,clomazone, CPMF, cresol, ortho-dichlorobenzene, dimepiperate, endothal,fluoromidine, fluridone, fluorochloridone, flurtamone, fluthiacet,indanofan, methazole, methyl isothiocyanate, nipyraclofen, OCH,oxadiargyl, oxadiazon, oxaziclomefone, pentachlorophenol, pentoxazone,phenylmercury acetate, pinoxaden, prosulfalin, pyribenzoxim, pyriftalid,quinoclamine, rhodethanil, sulglycapin, thidiazimin, tridiphane,trimeturon, tripropindan and tritac. The present invention contemplatesselecting herbicides from this list with water solubilities of about1000 ppm or less and formulating them as core-shell polyureameso-capsules. Preferable herbicides are those with water solubilitiesof about 100 ppm or less. More preferable herbicides are those withwater solubilities of 10 ppm or less. Herbicides can be chosen based onwater solubilities published in compendia such as The Pesticide ManualFourteenth Edition, ISBN 1-901396-14-2, which is incorporated herein byreference in its entirety. Future editions of The Pesticide Manual willalso be useful for selecting herbicides for incorporation intocore-shell polyurea mesocapsules.

Many classes and types of modifiers of plant physiology and structureare useful in agriculture. Examples include ancymidol,aminoethoxyvinylglycine, 6-benzylaminopurine, carvone,chlorflurenol-methyl, chlormequat chloride, cloxyfonac, 4-CPA,cyclanilide, cytokinins, daminozide, dikegulac, ethephon, flurenol,flurprimidol, forchlorfenuron, gibberellic acids, gibberellins,inabenfide, indol-3-ylacetic acid, 4-indol-3-ylbutyric acid, maleichydrazide, mepiquat chloride, 1-methylcyclopropene,2-(1-napthyl)acetamide, 1-napthylacetic acid, 2-napthyloxyacetic acid,nitrophenolates, paclobutrazol, N-phenylphthalamic acid,prohexadione-calcium, n-propyl dihydrojasmonate, thidiazuron, tribufos,trinexepac-ethyl, and uniconazole. The present invention contemplatesselecting growth regulators from this list with water solubilities ofabout 1000 ppm or less and formulating them as core-shell polyureameso-capsules. Preferable modifiers of plant physiology and structureare those with water solubilities of about 100 ppm or less. Morepreferable modifiers of plant physiology and structure are those withwater solubilities of 10 ppm or less. Modifiers of plant physiology andstructure can be chosen based on water solubilities published incompendia such as The Pesticide Manual Fourteenth Edition, ISBN1-901396-14-2, which is incorporated herein by reference in itsentirety. Future editions of The Pesticide Manual will also be usefulfor selecting modifiers of plant physiology and structure forincorporation into core-shell polyurea mesocapsules.

Mesocapsule formulations of herbicides in accordance with variousembodiments can be used in combination with a wide variety of herbicidesafeners, incuding safeners such as benoxacor, benthiocarb, brassinolide, cloquintocet (mexyl), cyometrinil, cyprosulfamide, daimuron,dichlormid, dicyclonon, dimepiperate, disulfoton, fenchlorazole-ethyl,fenclorim, flurazole, fluxofenim, furilazole, isoxadifen-ethyl,mefenpyr-diethyl, MG 191, MON 4660, naphthalic anhydride (NA),oxabetrinil, R29148 and N-phenylsulfonylbenzoic acid amides. The levelof active ingredient level in the oil phase used to synthetize theseformulations can range from about 0.001 wt. % to about to 99 wt. %. Thesafeners may be encapsulated in core-shell mesocapsules alone orincombination with suitable herbicides or they may be added to theformulation medium outside of the meso-capsule.

It is contemplated that mesoparticles of the present disclosure can beused with many conventional formulation ingredients such as aqueous ornon-aqueous solvent media or diluents in which the mesoparticles aresuspended or slurried at a concentration of the agricultural activeingredient, with respect to the formulation, from about 0.1% to about30%. Conventional inactive or inert ingredients such as dispersants,thickening agents, stickers, film-forming agents, buffers, emulsifiers,anti-freeezing agents, dyes, stablizers, solid carriers and the like mayalso be incorporated into formulations containing mesoparticles.

It is contemplated that formulations of agricultural AIs contained inmesocapsules can be utilized to control insects, mites, plant diseasesor weeds by providing and applying an agriculturally effective amount ofthe formulation to at least one of the following: the plant, plantfoliage, blossoms, stems, fruits, the area adjacent to the plant, soil,seeds, germinating seeds, roots, liquid and solid growth media, andhydroponic growth solutions, surface to be treated, and into or onto thepest itself. The mesocapsule formulation can be diluted in a suitableagricultural diluent, such as water, and applied by any conventionalmethod, including but not limited to: 1) application as a foliar spray,preferably in sufficient volume to wet the foliage or treatment surface,2) application as a drench to soil, 3) application to seeds, 4)application by injection into soil or hydroponic growth media, and 5)directly into or onto the pest. It is further envisioned thatmesocapsule formulations can be applied in mixture with conventionalformulations of agricultural AIs, plant nutrients and modifiers of plantphysiology and structure. Conventional formulations of agricultural AI'sinclude solutions such as oil in water or water in oil emulsifiableconcentrates and dispersions, solutions of AIs in water, sprayableconcentrates of AIs as suspended particulates with a volume averagediameter of about 1 micron or larger, AIs in the form of wettablepowders with a volume average diameter of about 1 micron or larger andAIs in the form of granules with a volume average diameter of about 10microns or larger.

EXAMPLES Particle Size Measurements

The particle size can be determined in particular by the known method ofquasi-elastic light scattering. One apparatus that can be used for thisdetermination is the Brookhaven 90Plus Nanoparticle Size Analyzer. Thisapparatus provides a measure of the average diameter by photoncorrelation spectroscopy (or PCS). In addition, the Malvern MasterSizer2000 may also be used for particle size measurements. Alternatively,particle size may be measured by other known techniques includingcentrifugation or electron microscopy.

Synthesis of Mesocapsules

Preparation of Stock Solutions of Amino Acids Used to SynthesizeMesocapsules.

Before the initiation of the various reaction runs used to synthesizethe exemplary mesocapsules disclosed herein, stock solutions of glycineand lysine were prepared in the proportions listed in FIG. 1.

General Methods Used to Prepare Some of the Polyurea MesocapsulesDisclosed Herein.

A typical method used to synthesize a representative polyureamesocapsule formulation is set forth below using the ingredients andquantities listed in FIG. 2. Briefly, fenbuconazole, benzyl acetate,hexadecane, and PAPI™ 27 polymeric MDI (The Dow Chemical Co.) were addedto a 60 ml jar and mixed until uniform. Surfactant, water, and glycinesolutions were added to the jar and mixed with a hand-heldBioHomogenizer mixer (BioSpec Products, Inc.) for about 10 seconds tocreate a pre-emulsion. The jar was placed in an ice bath and thepre-emulsion was sonicated for 5 minutes using a Branson 184VUltrasonicator at 40% power to create the final emulsion. A crosslinkerwas added to final emulsion to react with the polymeric MDI to createthe final product except for sample 4 in which the polymeric MDI wasallowed to react with water over time to create the final product. Theparticle volume-average diameter of meso-capsules in each sample wasmeasured using a Brookhaven 90Plus Nanoparticle Size Analyzer. Thevarious mesocapsule formulations listed in FIG. 2 were made using thesemethods. As indicated in FIG. 2, the compositions of the reactionmixtures were varied to create the various formulations disclosedherein. The formulations referenced in FIG. 4 were tested on plants todetermine their curative and preventative plant disease controlproperties.

A polyurea mesocapsule formulation containing fenbuconazole was preparedusing the ingredients described herein as wt % amounts relative to theentire formulation. The oil phase and aqueous phase were preparedseparately. In the oil phase were combined, 5.07 wt % of fenbuconazole,14.33 wt % of cyclohexanone and 14.08 wt % of Aromatic 200 solvent toprovide an initial solution. To the initial solution were added 1.31 wt% of Indopol™ H15 (INEOS Oligomers), 6.54 wt % of isophoronediisocyanate and 2.18 wt % of PAPI™ 27 (The Dow Chemical Company). Inthe aqueous phase were combined 42.56 wt % of water, 0.10 wt % ofProxel™ GXL (Arch UK Biocides, Ltd.) and 0.44 wt % of sodium laurylsulfate. The aqueous phase was combined with the oil phase while mixingwith a Silverson L4RT High Shear Mixer/Emulsifier at 6000 rpm for 2 minto make a pre-emulsion that was cooled in an ice/water bath. Thepre-emulsion was subsequently homogenized under high pressure withice/water cooling by an Emulsiflex®-C3 (Avestin, Inc., 600-1000 bar) tomake a stable oil-in-water emulsion at meso scale. With stirring, 0.87wt % of solid sodium lauryl sulfate was added, followed by the additionof 1.31 wt % of L-lysine (dry weight basis) as a 44.4 wt % solution inwater to react with PAPI™ 27, and the addition of 2.20 wt % ofdiethylenetriamine as a 25 wt % solution in diethylene glycol-water(0.76:0.24, wt %/wt %) in 1 hr to react with the isophoronediisocyanate. The mixture was allowed to stir at room temperature for 4hr to complete polyurea shell formation. The formulation containedmesocapsules of fenbuconazole with a particle volume average diameter of313 nm.

The following procedures were utilized to make mesocapsule suspensionsof 328255-92-1, epoxiconazole, atrazine, fluoroxypyr-meptyl, spinosadand indoxacarb. The oil phase and aqueous phase were prepared separatelyusing the ingredients and amounts shown in FIG. 3. The active ingredientwas dissolved in solvent/solvent mixtures to make 77% of the oil phase,followed by the addition of 3% ultrahydrophobe and 20% isocyanate(Monomer 1). Into the aqueous phase were added Proxel™ GXL (Arch UKBiocides, Ltd.; 0.1% of total formulation) and sodium lauryl sulfate (3%of oil phase). The aqueous phase was combined with the oil phase and themixture was magnetically stirred for 2 min to make a pre-emulsion, whichwas subsequently sonicated (4-5 min) using a Vibra Cell™ (Sonics &Materials, Inc.) sonicator at 750 W and 24-25% amplitude in an ice/waterbath to make a stable oil-in-water emulsion at meso scale. Uponstiffing, polyamine (Monomer 2) was added to react with the isocyanateto form the polyurea shell. The various mesocapsule formulations listedin FIG. 3 were made using these methods. The formulations referenced inFIG. 4 were tested on plants and insects to determine their pest controlproperties.

Aqueous suspension concentrate formulations of 328255-92-1,epoxiconazole and indoxacarb were prepared by conventional methods usingstandard surfactants, wetting agents and milling equipment to providesamples 7, 9 and 13 shown in FIG. 4. These samples had volume averagediameters of about 2.5 μm each.

Referring now to FIG. 4, the table includes a listing of some of theformulations that were tested on wheat leaf blotch. The polyureamesocapsules of fenbuconazole listed in FIG. 4 were tested to measuretheir curative and protectant effects on wheat leaf blotch disease,which is caused by the fungus, Septoria tritici. Measurements wereconducted on separate sets of wheat (cultivar Yuma) plants. The polyureameso-capsules made in accordance with various embodiments disclosedherein were compared to Indar™ 75WP, a commercially availableformulation of fenbuconazole. Each formulation of fenbuconazole wasdiluted in water and tested at the rates of 62.5, 20.8, 6.9, 2.3 and0.77 g active ingredient/Ha. Each experimental unit consisted of 8 to 10wheat plants grown in 5 cm by 5 cm pots of growth media comprised ofhalf MetroMix and half clay loam soil. Each treatment was replicatedthree times and treatments were randomized after chemicals were applied.

In the curative test, plants were inoculated in the 2-leaf stage ofgrowth two days before the test and control formulations were applied tothe plants. For the protectant test, the test and control formulationswere applied to the plants during the two leaf stage of growth andinoculated four days later with the fungi that causes leaf blotchdisease. Treatments were applied using a Gen III Research Sprayer(DeVries Mfg., Hollandale Minn.) tracksprayer equipped with a SprayingSystems 8002E TeeJet spray nozzle and calibrated to deliver 100 L/Ha.

Inoculum of the foliar pathogen, Septoria tritici, was prepared byharvesting conidia from freshly erumpent and mature pycnidia. An aqueoussuspension of conidia was made by counting several samples in ahaemocytometer and then adjusting the suspension to include about1,000,000 conidia/ml. Plants were inoculated by applying a fine mistwith a low pressure compressed air sprayer at a volume of approximately200 ml per 80 pots of wheat. After inoculation, plants were incubated ina dark dew room (22° C.) at 99-100% relative humidity for 24 hours, thenmoved to a lighted dew room (20° C.) at 99-100% relative humidity for anadditional 48 hrs and then placed in a greenhouse set at 20° C. and a14-hr photoperiod for the remainder of the test. Plant growth wasmaintained through regular application of dilute liquid fertilizersolution.

The wheat seedlings were rated for disease about 21 days after theinoculation. Percent disease was assessed by making a visual estimate ofthe percent of the leaf showing disease symptoms. Plants that were firstinoculated and then treated with chemical two days later providedindications of curative effects. Plants that were first treated and theninoculated four days later provide indications of protectant effects.The disease level measured on untreated plants in the curative test wasabout 82%. The disease level measured on untreated plants in theprotectant test was about 95%.

Referring now to FIGS. 5 and 6, the results of the various tests are asfollows. In the curative test (FIG. 5), all mesocapsule formulations offenbuconazole resulted in generally lower levels of disease whencompared to the standard wettable powder formulation of fenbuconazole.Similarly, in the protectant test (FIG. 6), mesocapsule formulations offenbuconazole resulted in lower levels of disease at one or more ratestested when compared to the standard wettable powder formulation.

Referring now to FIG. 4, the table includes a listing of some of theformulations that were tested on brown rust of wheat. The polyureamesocapsule formulations of 328255-92-1 and epoxiconazole listed in FIG.4 were tested to measure their protectant effects on the wheat diseaseknown as brown rust, which is caused by the fungus, Puccinia reconditaf. sp. tritici. Measurements were conducted on wheat (cultivar Yuma)plants. The polyurea mesocapsules made in accordance with variousembodiments disclosed herein were compared to conventional water-basedparticulate formulations. Each formulation was diluted in water andtested at the rates of 62.5, 20.8, 6.9, 2.3 and 0.77 g activeingredient/Ha. Each experimental unit consisted of 8 to 10 wheat plantsgrown in 5 cm by 5 cm pots of growth media comprised of half MetroMixand half clay loam soil. Each treatment was replicated four times andtreatments were randomized after chemicals were applied.

The test and control formulations were applied to the plants during thetwo leaf stage of growth and inoculated four days later with the brownrust fungus. Treatments were applied using a Gen III Research Sprayer(DeVries Mfg., Hollandale Minn.) tracksprayer equipped with a SprayingSystems 8002E TeeJet spray nozzle and calibrated to deliver 100 L/Ha.

Inoculum of the foliar pathogen, Puccinia recondita f.sp. tritici, wasprepared by harvesting urediospores from freshly erumpent and maturepustules. The final aqueous suspension of urediospores was made usingthe following procedure. 0.1 g of urediospores, added to three drops ofTween 20, and then mixed as a paste. To the paste was added 100 ml ofdistilled water. The suspension yielded approximately 1,000,000urediospores/ml. Plants were inoculated by applying a fine mist with alow pressure compressed air sprayer at a volume of approximately 300 mlper 80 pots of wheat. After inoculation, plants were incubated in a darkdew room (22° C.) at 99-100% relative humidity for 24 hr, then moved toa greenhouse set at 24° C. and a 14-hr photoperiod for the remainder ofthe test. Plant growth was maintained through regular application ofdilute liquid fertilizer solution.

The wheat seedlings were rated for disease approximately 7-8 days afterthe inoculation. Percent disease was assessed by making a visualestimate of the percent disease on the primary leaf. Results wereaveraged across rates. The test was performed twice and results of theindividual tests were combined.

Referring now to FIG. 7, the combined results of two protectant testswith brown rust indicate that mesocapsule formulations of 328255-92-1and epoxiconazole resulted in generally lower levels of disease whencompared to the standard sprayable concentrate formulations.

Referring now to FIG. 4 the table includes a listing of the formulationsthat were tested for the herbicidal active ingredients atrazine andfluoroxypyr-meptyl. The polyurea meso-formulations made in accordancewith various embodiments disclosed herein were compared to conventionalwater-based particulate formulations. The polyurea mesocapsuleformulations of atrazine and fluoroxypyr-meptyl listed in FIG. 4 weretested to measure their post-emergence herbicidal effects on variousdicot and monocot weed species utilizing the methods described herein.

A peat based potting soil, Metro-mix 360, was used as the soil media forthis test. Metro-mix is a growing medium consisting of 35 to 45%specially processed coconut coir pith, 10 to 20% horticultural gradevermiculite, 15 to 25% processed ash bark, 20 to 30% choice CanadianSphagnum Peat Moss and proprietary nutrients and other ingredients.Several seeds of each species were planted in 10 cm square pots and topwatered twice daily. Casia obtusifolia (CASOB), Abutilon theophrasti(ABUTH), Sida spinosa (SIDSP), Setaria faberi (SETFA), Digitaria sativa(DIGSA), Kochia scoparia (KCHSC), Stellaria media (STEME), Polygonumconvolvulus (POLCO), Chenopodium album (CHEAL) and Ambrosiaartemisiifolia (AMBEL) were propagated in the greenhouse at a constanttemperature of 26 to 28° C. and 50 to 60% relative humidity. Naturallight was supplemented with 1000-watt metal halide overhead lamps withan average illumination of 500 uE m-2 s-1 photosynthetic activeradiation (PAR). The photoperiod was 16 hr. Plant material wastop-watered prior to treatment and sub-irrigated after treatment.

The mesocapsule formulation of atrazine was compared to a standard waterdispersable granule commercial formulation, AAtrex Nine-0™ (Syngenta).The two formulations of atrazine were diluted in de-ionized water andapplied at the rates of 2240, 1120, 460 and 280 g active ingredient/Ha.The mesocapsule formulation of fluoroxypyr-meptyl was compared to astandard commercial fluoroxypyr-meptyl formulation, Casino™ 25WP (DowAgroSciences, LLC). The two formulations of fluoroxypyr-meptyl werediluted in de-ionized water and applied at the rates of 200, 100, 50, 25and 12.5 g active ingredient/Ha. Treatments were applied with atracksprayer manufactured by Allen Machine Works. The sprayer utilizedan 8002E spray nozzle, spray pressure of 262 kPa pressure and speed of1.5 mph to deliver 187 L/Ha. The nozzle height was 46 cm above the plantcanopy. The growth stage of the various weed species ranged from 2 to 4leaf. Treatments were replicated 3 times. Plants were returned to thegreenhouse after treatment and sub-watered throughout the duration ofthe experiment. Plant material was fertilized twice weekly withHoagland's fertilizer solution. Visual assessments of percent controlwere made on a scale of 0 to 100% as compared to the untreated controlplants (where 0 is equal to no control and 100 is equal to completecontrol).

Referring now to FIG. 8 the results of the post-emergence herbicide testindicate that mesocapsule formulation of atrazine resulted in generallyhigher levels of control when compared to the standard water dispersablegranule formulation.

Referring now to FIG. 9 the results of the post-emergence herbicide testindicate that mesocapsule formulation of fluoroxypyr-meptyl resulted ingenerally higher levels of control when compared to the standardwettable powder formulation.

Referring now to FIG. 4, the table includes a listing of theformulations that were tested for the insecticidal active ingredientindoxacarb. The polyurea mesocapsule formulation of indoxacarb (Sample12) listed in FIG. 4 was tested to measure the effects on 2^(nd) instardiamondback moth larvae (Plutella xylostella) and male adult Germancockroach (Blatella germanica) mortality and leaf disk or baitconsumption, respectively. The indoxacarb polyurea mesocapsuleformulation made in accordance with various embodiments disclosed hereinwas compared to a suspension concentrate water based formulation ofindoxacarb (Sample 13).

Each formulation of indoxacarb was diluted in water for testing. Ratestested for mortality and treated leaf disk consumption for diamondbackmoth were 0.15, 0.62, 2.5, 10, 20, 40, 80, and 160 ppm. Rates tested formortality and treated water based bait for German cockroach were0.0001%, 0.001%, 0.01%, 0.1%, and 1% depending on the type of test (ieinjection, topical application or ingestion of water based bait).

For the Diamondback moth test, cabbage plants were grown in thegreenhouse and were trimmed to 2 leaves per plant. Formulations werediluted using deionized water plus addition of 0.025% Silwet L-77surfactant. Tested rates were 0.15, 0.62, 2.5, 10, 20, 40, 80, and 160ppm. Cabbage plants were sprayed using a track sprayer deliveringapproximately 200 liters/hectare spray volume. After the treated cabbageplants dried, leaf discs were taken from each sprayed plant and 1 leafdisk was placed in each well of a 32 well bioassay tray which containeda thin layer of agar at the bottom of the well. Three 2^(nd) instardiamondback moth larvae were placed in the center of each leaf disc andthe tray was covered with a plastic lid. Data on mortality and percentleaf disk consumed was collected at various time intervals from 1-4days.

Referring now to FIGS. 10 and 11, the results of the diamondback mothtest are as follows. Differences were noted in favor of the polyureamesocapsule formulation at the rates of 2.5 and 10 ppm.

At the 2.5 ppm rate, the polyurea mesocapsule formulation treatmentreduced the amount of treated leaf disc consumption by 28-46 percent at3 and 4 days post-treatment, respectively, as compared to the waterbased suspension concentration formulation treatment. At the 10 ppmrate, the polyurea meso-formulation treatment reduced the amount oftreated leaf disc consumption by 18-37% at 3 and 4 days post-treatment,respectively, as compared to the water based suspension concentrationformulation treatment. This decreased amount of treated leaf diskconsumption indicates the indoxacarb polyurea mesocapsule formulationwas able to protect the treated cabbage plant from feeding bydiamondback moth larvae better than a water based suspensionconcentration formulation of indoxacarb.

At the 10 ppm rate at 4 days post-treatment, the polyurea mesocapsuleformulation treatment increased the amount of diamondback moth larvaemortality 19% as compared to the water based suspension concentrationformulation treatment. This increased mortality indicates the indoxacarbpolyurea meso-formulation was able to enhance toxic activity at the 10ppm rate over the water based suspension concentration formulation ofindoxacarb.

Three types of tests were conducted for German cockroach—injection,topical and ingestion bioassay. For the injection test, 10 male adultGerman cockroachs per treatment were injected with 1 ul of eachtreatment. Treatments solutions were made by diluting indoxacarbformulations in Milli-Q purified water to produce indoxacarbconcentrations of 0.001%, 0.01%, 0.1% and 1%. The injected cockroacheswere held in 100×25 mm petri dishes containing food and water and placedin a laboratory controlled environment chamber at 26° C. and 60%relative humidity. The injected cockroaches were checked daily for 7days and the number dead were recorded. Food and water was refreshed asneeded.

Referring now to FIG. 12, the results of the German cockroach injectiontest are as follows for percent mortality where differences were notedin favor of the polyurea meso-formulation. Differences between theformulations tested were noted at the 0.01% rate.

At the 0.01% concentration of indoxacarb at 2-7 days post-treatment, thepolyurea mesocapsule formulation treatment increased the amount ofGerman cockroach mortality by 20-30% as compared to the water basedsuspension concentration formulation treatment. This increased mortalityindicates that indoxacarb in the polyurea mesocapsule formulation hadgreater efficacy at the 0.01% rate compared to the suspensionconcentrate formulation of indoxacarb.

The mortality expression of the formulations was tested when water baseddilutions of the formulations were directly applied to Germancockroaches in a topical bioassay. For the topical test, 10 adult maleGerman cockroaches per treatment received 1 ul of each treatmenttopically applied to the pronotum via syringe. Cockroaches wereanesthetized with CO₂ before and after treatment. Formulations weretested in Milli-Q-purified water dilutions yielding indoxacarbconcentrations of 0.001%, 0.01%, 0.1% and 1%. The treated cockroacheswere held in 60×15 mm petri dishes (one per dish) containing food andwater in a laboratory controlled environment chamber. The treatedcockroaches were checked daily for 7 days and the number dead wererecorded. Food and water was refreshed as needed.

Referring now to FIG. 13, the results of the German cockroach topicaltest are as follows for percent mortality where differences were notedin favor of the polyurea meso-formulation. Differences between theformulations tested were noted at the 0.1% rate only.

At the 0.1% rate at 1-7 days post-treatment, the polyurea mesocapsuleformulation treatment increased the amount of German cockroach mortalityby 20-40% as compared to the water based suspension concentrateformulation treatment. This increased mortality indicates the indoxacarbpolyurea mesocapsule formulation was able to enhance toxic activity atthe 0.1% rate over the water based suspension concentrate formulation ofindoxacarb. In addition, the polyurea mesocapsule formulation treatmentalso increased the speed of mortality as compared to the water basedsuspension concentrate formulation treatment of indoxacarb.

The ingestion bioassay was used to test mortality expression of theformulations when water based dilutions were ingested by Germancockroaches. For the ingestion test, 10 adult male German cockroachesper 5 reps were placed into 100×25 mm petri dishes with a smallcardboard harborage and a piece of Purina™ dog chow for food.Cockroaches were deprived of water for 3 days prior to exposure to thewater based treated bait. Exposure to the water based treated bait was ano choice exposure for 30 minutes on days 1-3 where on day one 200 ul ofbait was provided and on days two and three 150 ul of bait was provided.The water bait provided on day one was removed and replaced with newwater bait on days 2 and 3. After the 3 days exposure to the water bait,the cockroaches were provided untreated water and food for the next 11days. Formulations were diluted indeionized yielding indoxacarbconcentrations of 0.0001%, 0.001%, 0.01%, and 0.1%. The treatedcockroaches were checked daily for 15 days and the number dead wererecorded. Quantity of water bait consumed was recorded for the 3 daysthis exposure occurred.

There were no differences between the formulations tested for percentmortality where the polyurea meso-formulation outperformed the waterbased suspension concentration formulation treatment of indoxacarb.However, at the 0.1% rate there were differences noted for baitconsumption data. Referring now to FIG. 14, the results of the Germancockroach ingestion test are as follows for mg consumption at the 0.1%rate.

At the 0.1% rate at 1 day post-treatment, the polyurea mesocapsuleformulation bait treatment decreased the amount of bait consumption byGerman cockroaches by 86 mg as compared to the water based suspensionconcentration formulation bait treatment. This decreased consumption ofthe indoxacarb bait at the 0.1% concentration of indoxacarb in thepolyurea mesocapsule formulation indicates quicker feedingreduction/cessation at day 1 compared to the water based suspensionconcentration formulation of indoxacarb.

While the novel technology has been illustrated and described in detailin the figures and foregoing description, the same is to be consideredas illustrative and not restrictive in character, it being understoodthat only the preferred embodiments have been shown and described andthat all changes and modifications that come within the spirit of thenovel technology are desired to be protected. As well, while the noveltechnology was illustrated using specific examples, theoreticalarguments, accounts, and illustrations, these illustrations and theaccompanying discussion should by no means be interpreted as limitingthe technology. All patents, patent applications, and references totexts, scientific treatises, publications, and the like referenced inthis application are incorporated herein by reference in their entirety.

We claim:
 1. A composition for the delivery of an agricultural activeingredient, comprising: a water phase; and a core-shell mesocapsule, themesocapsule having a polymer shell surrounding a core within the polymershell, the polymer shell having a hydrophilic outer surface at leastpartially in contact with the water phase, wherein the polymer shell iscomprised of polyurea; and wherein at least a portion of the poorlywater soluble agriculturally active ingredient is included in an oilphase in the core, the mesocapsule having a volume-average particlediameter between about 30 nm and about 500 nm and wherein the oil phasecomprises about 1 wt. % to about 60 wt. % of the total weight of thecomposition wherein the polymer shell is further comprised of a compoundhaving a first functional moiety and a second functional moiety, whereinthe first functional moiety is selected from a primary amine, asecondary amine, a primary amino group, and a secondary amino group, andthe second functional moiety is selected from the group consisting ofcarboxylate and trimethylamine.
 2. The composition according to claim 1,wherein the polyurea is a reaction product of at least onepolyisocyanate and at least one polyamine.
 3. The composition accordingto claim 1, wherein the mesocapsule has a volume average diameter in therange of about 50 nm to about 300 nm.
 4. The composition according toclaim 1, wherein the shell includes hydrophilic functional groups and atleast some of the hydrophilic functional groups contact water.
 5. Thecomposition according to claim 4, wherein the hydrophilic functionalgroup on the surface of the shell is a carboxylate.
 6. The compositionaccording to claim 1 wherein the active ingredient has solubility inwater of about 1,000 parts per million or less.
 7. The compositionaccording to claim 1, wherein the agriculturally active ingredient isselected from the group consisting of a herbicide, an insecticide, and afungicide.
 8. The composition according to claim 1, wherein theagriculturally active ingredient is selected from the group consistingof fenbuconazole, (3S,6S,7R,8R)-8-benzyl-3-(3-(isobutyryloxymethoxy)-4-methoxypicolinamido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-ylisobutyrate, epoxiconazole, atrazine, fluoroxypry-meptyl, spinosad, andindoxacarb.
 9. The composition according to claim 1, wherein thecomposition comprises essentially no surfactant.
 10. The compositionaccording to claim 1, wherein the composition comprises less than 1 wt.% surfactant based on the weight of the oil phase.
 11. The compositionaccording to claim 1, wherein the composition comprises less than 0.5wt. % surfactant based on the weight of the oil phase.
 12. Thecomposition according to claim 1, wherein the composition comprises nosurfactant.
 13. The composition according to claim 1, wherein thecompound is selected from glycine, a salt of glycine, or a mixture ofglycine and a salt of glycine.
 14. The composition according to claim 1,wherein the agriculturally active ingredient comprises about 1.19 wt. %to about 5.73 wt. % of the total weight of the composition.
 15. Acomposition for the delivery of an agricultural active ingredient,comprising: a water phase; a core-shell mesocapsule, the mesocapsulehaving a polymer shell comprised of polyurea and a compound having afirst functional moiety and a second functional moiety, wherein thefirst functional moiety is selected from the group consisting of aprimary amine, mine a primary amino group, and a secondary amino group,and the second functional moiety is selected from the group consistingof carboxylate and trimethylamine, the mesocapsule having a hydrophilicouter surface at least partially in contact with the water phase; an oilphase comprising a poorly water soluble agricultural active ingredient,wherein at least a portion of the poorly water soluble agriculturallyactive ingredient is included in a core within the polymer shell, themesocapsule having a volume-average particle diameter between about 30nm and about 500 nm.
 16. The composition according to claim 15, whereinthe compound is selected from glycine, a salt of glycine, or a mixtureof glycine and a salt of glycine.
 17. The composition according to claim15, wherein the composition comprises essentially no surfactant.
 18. Thecomposition according to claim 15, wherein the composition comprisesless than 1 wt. % surfactant based on the weight of the oil phase. 19.The composition according to claim 15, wherein the composition comprisesless than 0.5 wt. % surfactant based on the weight of the oil phase. 20.The composition according to claim 15, wherein the composition comprisesno surfactant.
 21. The composition according to claim 15, wherein theoil phase further includes between about 1 wt. % to about 90 wt. % of anorganic solvent having a water solubility of about 10 g/100 ml or less.22. The composition according to claim 15, wherein the oil phase furtherincludes between about 0.5 wt. % to about 10 wt. % of anultrahydrophobe.
 23. A method of controlling insects, mites, plantdiseases or weeds including the steps of: providing a formulationincluding the composition of claim 1, and applying an agriculturallyeffective amount of the formulation to at least one of the following:the plant, plant foliage, blossoms, stems, fruits, the area adjacent tothe plant, soil, seeds, germinating seeds, roots, liquid and solidgrowth media, hydroponic growth solutions, treated surfaces, and intoand onto the pest itself.
 24. A method of controlling insects, plantsdiseases or weeds including the steps of: providing a formulationincluding the composition of claim 1, and applying an agriculturallyeffective amount of the formulation in mixture with one or moreconventional formulations of agricultural active ingredients ornutrients to at least one of the following: the plant, plant foliage,blossoms, stems, fruits, the area adjacent to the plant, soil, seeds,germinating seeds, roots, liquid and solid growth media, hydroponicgrowth solutions, treated surfaces, and into and onto the pest itself.